This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

1. Name of the medicinal product

Trumenba suspension for injection in pre-filled syringe

Meningococcal group B vaccine (recombinant, adsorbed)

2. Qualitative and quantitative composition

1 dose (0.5 ml) contains:

Neisseria meningitidis serogroup B fHbp subfamily A1,2,3

Neisseria meningitidis serogroup B fHbp subfamily B1,2,3

60 micrograms

60 micrograms

1 Recombinant lipidated fHbp (factor H binding protein)

2 Produced in Escherichia coli cells by recombinant DNA technology

3 Adsorbed on aluminium phosphate (0.25 milligram aluminium per dose)

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Suspension for injection.

White liquid suspension.

4. Clinical particulars

4.1 Therapeutic indications

Trumenba is indicated for active immunisation of individuals 10 years and older to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B.

See section 5.1 for information on the immune response against specific serogroup B strains.

The use of this vaccine should be in accordance with official recommendations.

3 doses: 2 doses (0.5 ml each) administered at least 1 month apart, followed by a third dose at least 4 months after the second dose (see section 5.1).

Booster dose

A booster dose should be considered following either dosing regimen for individuals at continued risk of invasive meningococcal disease (see section 5.1).

Other paediatric population

Safety and efficacy of Trumenba in children below 10 years of age have not been established. No data are available.

Method of administration

For intramuscular injection only. The preferred site for injection is the deltoid muscle of the upper arm.

For instructions on the handling of the vaccine before administration, see section 6.6.

There are no data available on the interchangeability of Trumenba with other meningococcal group B vaccines to complete the vaccination series.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

In order to improve the traceability of biological medicinal products, the tradename and batch number of the administered product should be clearly recorded (or stated) in the patient file.

Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.

As with other injectable vaccines, syncope (fainting) can occur in association with administration of Trumenba. Procedures should be in place to avoid injury from fainting.

Vaccination should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, should not result in the deferral of vaccination.

Do not inject intravenously, intradermally, or subcutaneously.

Trumenba should not be given to individuals with thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection, unless the potential benefit clearly outweighs the risk of administration.

As with any vaccine, vaccination with Trumenba may not protect all vaccine recipients.

Limitations of clinical trials

There are no data on the use of Trumenba in immunocompromised individuals. Immunocompromised individuals, including individuals receiving immunosuppressant therapy, may have a diminished immune response to Trumenba.

There are no data on the use of Trumenba in subjects above 65 years of age.

4.5 Interaction with other medicinal products and other forms of interaction

When given concomitantly with other vaccines Trumenba must be administered at a separate injection site.

Trumenba should not be mixed with other vaccines in the same syringe.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of Trumenba in pregnant women. The potential risk for pregnant women is unknown. Nevertheless, vaccination should not be withheld when there is a clear risk of exposure to meningococcal infection.

Reproduction studies performed in female rabbits have revealed no evidence of impaired female fertility or harm to the foetus due to Trumenba.

Breast-feeding

It is unknown whether Trumenba is excreted in human milk. Trumenba should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to fertility in females (see section 5.3).

Trumenba has not been evaluated for impairment of fertility in males.

4.7 Effects on ability to drive and use machines

Trumenba has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of the safety profile

The safety profile presented is based on analysis of over 15,000 subjects (aged 10 years and older) who have been vaccinated with at least 1 dose of Trumenba in 11 completed clinical studies. The most common adverse reactions observed were injection site pain, redness and swelling at the vaccination site, headache, fatigue, chills, diarrhoea, muscle pain, joint pain, and nausea.

Adverse reactions following booster vaccination in 268 subjects aged 15 to 23 years were similar to adverse reactions during the primary Trumenba vaccination series approximately 4 years earlier.

List of adverse reactions

Adverse reactions reported in clinical studies are listed in decreasing order of frequency and seriousness according to the following frequency categories:

* The following is considered an adverse reaction for Trumenba and was reported in the postmarketing experience. Because this reaction was derived from spontaneous reports, the frequency could not be determined and is thus considered as not known.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

United Kingdom

Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Experience of overdose is limited. In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: vaccines; ATC code: J07AH09

Mechanism of action

Trumenba is a vaccine composed of 2 recombinant lipidated factor H binding protein (fHbp) variants. fHbp is found on the surface of meningococcal bacteria and is essential for bacteria to avoid host immune defenses. fHbp variants segregate into 2 immunologically distinct subfamilies, A and B, and over 96% of meningococcal serogroup B isolates in Europe express fHbp variants from either subfamily on the bacterial surface.

Immunisation with Trumenba, which contains one fHbp variant each from subfamily A and B, is intended to stimulate the production of bactericidal antibodies that recognize fHbP expressed by meningococci. The Meningococcal Antigen Surface Expression (MEASURE) assay was developed to relate the level of fHbp surface expression to killing of meningococcal serogroup B strains in serum bactericidal assays with human complement (hSBAs). A survey of over 2,150 different invasive meningococcal serogroup B isolates collected from 2000-2014 in 7 European countries, the US and Canada demonstrated that over 91% of all meningococcal serogroup B isolates expressed sufficient levels of fHbp to be susceptible to bactericidal killing by vaccine-induced antibodies.

Clinical efficacy

The efficacy of Trumenba has not been evaluated through clinical trials. Vaccine efficacy has been inferred by demonstrating the induction of serum bactericidal antibody responses to 4 meningococcal serogroup B test strains (see the Immunogenicity section).The 4 test strains express fHbP variants representing the 2 subfamilies (A and B) and, when taken together, are representative of meningococcal serogroup B strains causing invasive disease.

Immunogenicity

Protection against invasive meningococcal disease is mediated by serum bactericidal antibodies to bacterial surface antigens. Bactericidal antibodies act in concert with human complement to kill meningococci. This process is measured in vitro with serum bactericidal assay using human complement (hSBA) for meningococcal serogroup B. An hSBA titre of greater than or equal 1:4 is assumed to be protective against meningococcal disease. In the immunogenicity analysis for Trumenba, a response was defined as an hSBA titre of at least 1:8 or 1:16 depending on the hSBA strain. A 4-fold increase in hSBA titre for each of the 4 primary meningococcal serogroup B test strains was defined as follows: (1) For subjects with a baseline hSBA titre < 1:4, a 4-fold response was defined as an hSBA titre ≥ 1:16. (2) For subjects with a baseline hSBA titre ≥ 1:4, a 4-fold response was defined as an hSBA titre ≥ 4 times the lower limit of quantitation or ≥ 4 times the baseline titre, whichever was higher. A composite response was defined as a response for all 4 hSBA strains combined.

The immunogenicity of Trumenba following 2 or 3 vaccinations was evaluated in individuals 11 to 18 years of age in Europe (Study B1971012) and following 3 vaccinations in individuals 10 to 25 years of age globally (Studies B1971009 and B1971016).

In Study B1971012, Trumenba was administered according to the following schedules: Group 1 (0, 1, and 6 months); Group 2 (0, 2, and 6 months); Group 3 (0 and 6 months); Group 4 (0 and 2 months); Group 5 (0 and 4 months). Of the 1,713 subjects randomised, 427 were in Group 1, 430 were in Group 2, 427 were in Group 3, 286 were in Group 4, and 143 were in Group 5. All subjects received 4 study injections, either 2 or 3 doses of Trumenba and 1 or 2 doses of saline. The hSBA responses observed after the second or third dose for Groups 1, 2, and 3 are presented in Tables 1 and 2.

For the second and third doses, serum was obtained approximately 1 month after the second or third vaccination dose.

Table 1: Immune Responses Among Individuals 11 to 18 Years of Age Administered Trumenba After Various 2- and 3-Dose Schedules (Study B1971012)

Study B1971009 was a Phase 3, randomised, active-controlled, observer-blinded, multicentre trial in which subjects aged 10 to 18 years received 1 of 3 lots (Groups 1, 2, and 3) of Trumenba or the active control hepatitis A virus (HAV) vaccine/saline. A total of 2,693 subjects received at least 1 dose of Trumenba and 897 received at least 1 dose of HAV vaccine/saline. The study assessed the safety, tolerability, immunogenicity, and demonstration of manufacturability of 3 lots of Trumenba administered on a 0-, 2-, and 6-month schedule. The hSBA responses observed after the third dose in Group 1 are presented in Tables 3 and 4. Results from Groups 2 and 3 are not presented, as only 2 representative strains were evaluated. Similar results were observed in Groups 2 and 3 as observed in Group 1.

Study B1971016 was a Phase 3, randomised, placebo-controlled, observer-blinded, multicentre trial in which subjects 18 to 25 years of age were assigned to 2 groups in a 3:1 ratio (Group 1:Group 2). Group 1 received Trumenba at months 0, 2, and 6. Group 2 received saline at months 0, 2, and 6. A total of 2,471 subjects received Trumenba and 822 received saline. The hSBA responses observed after the third dose in Groups 1 and 2 are presented in Tables 3 and 4.

Serum was obtained approximately 1 month after vaccination.

Table 3. Immune Responses Among Individuals 10 to 25 Years of Age 1 Month Following the Third Dose of Trumenba or Control Given on a 0-, 2-, 6-Month Schedule (Study B1971009 and Study B1971016)

In Studies B1971009 and B1971016, the proportion of subjects achieving a defined hSBA titre after 3 doses of Trumenba, administered on a 0-, 2-, and 6-month schedule, was evaluated against a panel of 10 additional strains, each expressing a different fHbp variant (Table 5). These additional hSBAs support and extend the breadth of vaccine coverage demonstrated by the 4 representative primary strains (Tables 3 and 4).

Serum was obtained approximately 1 month after vaccination.

Table 5. Immune Responses Among Individuals 10 to 25 Years of Age Against 10 Additional Strains 1 Month Following the Third Dose of Trumenba Given on a 0-, 2-, 6-Month Schedule (Study B1971009 and Study B1971016)

Study B1971033 is an open-label, follow-up study of subjects previously enrolled in a primary study, including Study B1971012. Subjects attended visits over 4 years for collection of blood samples and received a single booster dose of Trumenba approximately 4 years after receipt of a primary series of 2 or 3 doses of Trumenba. The hSBA responses for subjects enrolled from primary Study B1971012 Group 1 (0-, 1-, 6-Month Schedule), Group 2 (0-, 2-, 6-Month) and Group 3 (0-, 6-Month) are presented in Tables 6 and 7. A booster response in hSBA responses at 1 month following a dose of Trumenba approximately 4 years after a primary series of 2 doses (Group 3) or 3 doses (Groups 1 and 2) was observed.

Table 6: Persistence of Immune and Booster Responses Among Individuals 11 to 18 Years of Age Administered a Primary Series of Trumenba on a 0-, 1-, 6-Month-; 0-, 2-, 6-Month- and 0-, 6-Month Schedule and a Booster 4 Years After Primary Series (Study B1971033)

Note: The lower limit of quantitation is an hSBA titre = 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).

Table 7: Persistence of Immune and Booster Responses Among Individuals 11 to 18 Years of Age Administered a Primary Series of Trumenba on a 0-, 1-, 6-Month-; 0-, 2-, 6-Month- and 0-, 6-Month Schedule and a Booster 4 Years After Primary Series (Study B1971033)

The European Medicines Agency has deferred the obligation to submit the results of studies with Trumenba in one or more subsets of the paediatric population for prevention of invasive meningococcal disease caused by N. meningitidis serogroup B (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data revealed no special hazard for humans based on conventional studies of repeated dose toxicity and reproduction and developmental toxicity.

6. Pharmaceutical particulars

6.1 List of excipients

Sodium Chloride

Histidine

Polysorbate 80 (E433)

Water for injections

For adsorbent, see section 2.

6.2 Incompatibilities

Do not mix Trumenba with other vaccines or medicinal products in the same syringe.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

4 years.

6.4 Special precautions for storage

Store in a refrigerator (2 °C-8 °C).

Syringes should be stored in the refrigerator horizontally to minimize the re-dispersion time.

Do not freeze.

6.5 Nature and contents of container

0.5 ml suspension in a pre-filled syringe (Type I glass) with plastic Luer Lok adapter, chlorobutyl rubber plunger stopper, and a synthetic isoprene bromobutyl rubber tip cap with a plastic rigid tip cap cover with or without needle. The tip cap and rubber plunger of the pre-filled syringe are not made with natural rubber latex.

Pack sizes of 1, 5, and 10 pre-filled syringes, with or without needle.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

During storage, a white deposit and clear supernatant may be observed in the pre-filled syringe containing the suspension.

Before use, the pre-filled syringe should be shaken vigorously to ensure that a homogeneous white suspension is obtained.

Do not use the vaccine if it cannot be re-suspended.

The vaccine should be visually inspected for particulate matter and discoloration prior to administration. In the event of any foreign particulate matter and/or variation of physical aspect being observed, do not administer the vaccine.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

8. Marketing authorisation number(s)

EU/1/17/1187/001

EU/1/17/1187/002

EU/1/17/1187/003

EU/1/17/1187/004

EU/1/17/1187/005

EU/1/17/1187/006

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 24th May 2017

10. Date of revision of the text

11/2018

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.